rs41283391

chr17-7017569-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572453.1(MIR497HG):n.2091G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 692,550 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (285 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1030 hom.)
• Consequence: MIR497HG ENST00000572453.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

Genes affected

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

C17orf49 (HGNC:28737): (chromosome 17 open reading frame 49) Enables identical protein binding activity. Predicted to be involved in chromatin organization. Located in cytosol and nucleoplasm. Part of MLL1 complex and NURF complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR195 (HGNC:31566): (microRNA 195) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

RNASEK-C17orf49 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR497HG	NR_038310.1	n.278-181G>A		intron_variant, non_coding_transcript_variant
C17orf49	NM_174893.4			downstream_gene_variant		ENST00000439424.6
MIR195	NR_029712.1			downstream_gene_variant
RNASEK-C17orf49	NR_037717.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR497HG	ENST00000572453.1	n.2091G>A		non_coding_transcript_exon_variant	1/1
C17orf49	ENST00000439424.6			downstream_gene_variant		1	NM_174893.4
MIR195	ENST00000385194.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9264 AN: 152220 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0635

GnomAD3 exomes AF: 0.0516 AC: 10367 AN: 200770 Hom.: 342 AF XY: 0.0518 AC XY: 5594 AN XY: 107972

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.0397

Gnomad EAS exome AF: 0.000516

Gnomad SAS exome AF: 0.0354

Gnomad FIN exome AF: 0.0705

Gnomad NFE exome AF: 0.0671

Gnomad OTH exome AF: 0.0586

GnomAD4 exome AF: 0.0565 AC: 30499 AN: 540212 Hom.: 1030 Cov.: 2 AF XY: 0.0564 AC XY: 16636 AN XY: 294750

Gnomad4 AFR exome AF: 0.0652

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0410

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.0357

Gnomad4 FIN exome AF: 0.0701

Gnomad4 NFE exome AF: 0.0676

Gnomad4 OTH exome AF: 0.0594

GnomAD4 genome AF: 0.0608 AC: 9264 AN: 152338 Hom.: 285 Cov.: 32 AF XY: 0.0592 AC XY: 4409 AN XY: 74490

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.0655

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0656 Hom.: 55

Bravo AF: 0.0611

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.5
Dann	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41283391; hg19: chr17-6920888;